A major limiting factor in previous studies of both the asymptomatic and pathological knee is the inability to non-invasively measure three-dimensional skeletal and muscular motion simultaneously. Cine phase contrast (PC) MRI (dynamic MRI) is the only technique currently available that can do just this. Cine-PC MRI, which is a combination of cine and phase contrast MRI, provides a temporal series of anatomic images of all cyclically moving and static structures in the imaging plane. Therefore, the overall goal of this work is to determine the specific sources of maltracking patterns in patellofemoral (PF) pain. As part of this overall goal, the purpose of this study is to determine how the loss of function in the vasti medialis muscle alters the dynamic control of patellar kinematics in healthy individuals, using cine-PC as the primary measurement tool. Twenty-three asymptomatic volunteers with no prior history of knee pain, trauma, leg surgery, or contraindications to having an MRI have been enrolled. During the first visit, the PF and tibiofemoral (TF) kinematics were derived from dynamic cine phase contrast velocity data. If the first visit data revealed the presence of a valid exclusion criteria, the subject was removed from the study (n=5, based on the presence of abnormal PF kinemtics); if not, the subject was asked to return within a week for the second segment of the study. For the second visit, the same kinematics were acquired immediately after administering a motor branch block to the VM using 3-5cc of 1% lidocaine. A repeated measures analysis of variance (ANOVA) was used to test the null hypothesis that the post- and pre-injection kinematics were no different across the knee angles of extension. A Kolmogorov-Smirnov test for normality was run. If the data were normally distributed, a repeated measures ANOVA was run using Hotellings T2 test statistic; if not, the non-parametric Friedman's test statistic was used. Upon rejection of the null hypothesis a post-hoc analysis (Wilcoxon signed rank test) was completed to determine at which knee angles the null hypothesis could be rejected. Pearsons correlations between the change in kinematics post-injection and the pre-injection kinematics were quantified at these same knee angles. This was followed by a step-wise linear regression. Significance was set at p0.05. Post-injection, the maximum lateral shift of the patellar and tibial origins (1.8mm, SD=1.7mm, p=0.003 KA=20 and 2.1mm, SD=2.9mm, p=0.02, KA = 15) and the maximum external tibial rotation (3.7, SD=4.4, p=0.006, KA=20) occurred at similar points in the extension arc. These changes were 3.2 to 4.8 times greater than the subject repeatability. The value of PF tilt trended laterally post-I (max=1.6, KA =15), but significant differences pre- to post-I were not found. No individual reported pain, based on a Visual Analog Scale, following the kinematic trials during visit 1 and visit 2. The lateral shift of the PF origin post-I was significantly correlated with the initial value of PF origins superior displacement in terminal extension (Pearson correlation coefficients (r-values) ranged from 0.47 to 0.48 for knee angles ranging from 10-20, p<0.05). To relate the kinematic changes seen following a VM block to those seen in PFPS, it is important to understand that there are likely subgroups within the PFPS population, each with unique kinematic alterations of varying etiologies. In a previous study the PFPS cohort was divided into two groups, lateral and non-lateral maltrackers. The lateral maltrackers demonstrated increased PF lateral and superior shift, lateral tilt, flexion, and valgus rotation. The change in kinematics following the nerve block could account for a portion of the lateral shift and tilt seen in the lateral maltrackers. Increased ligament laxity likely would have increased this shift and tilt, as well as increased the patellar ligament length, resulting in the observed PF superior shift (patella alta) in the lateral maltrackers. Patella alta reduces the influence of the femoral groove on PF kinematics in terminal extension, resulting in increased PF lateral shift (as supported by the correlations within this study), lateral tilt, and valgus rotation. Therefore, a combination of VM weakness and generalized ligament laxity could account for the kinematic variations in the lateral maltracking group. These changes would result in higher contact stresses when the patella is forced to re-engage with the femoral sulcus in early flexion and would reduce the overall contact area, both of which would likely leading to PF pain. The non-lateral maltrackers demonstrated increases in PF flexion and TF internal rotation only, with a trend towards PF medial translation and medial tilt. A larger LTI combined with a normative PF superior location in the non-lateral maltrackers limited lateral PF shift and influenced patellar tilt in this subgroup. Thus, in this sub-group a loss of VM strength likely would have resulted in increased contact force between the lateral femoral sulcus and the patella, resulting in PF pain, without excessive lateral shift and tilt being present. The high LTI and the trend towards medial tilt in the non-lateral maltracking group may help explain the variability in the post-I change in PF lateral tilt. In the presence of a high LTI, a loss of strength in the VMO strength could result in the lateral patellar edge riding up the lateral femoral sulcus, resulting in the observed trend towards medial tilt in the non-lateral maltrackers and the post-I medial tilt observed in some subjects. The current study provides crucial data for validation of musculoskeletal modeling. Specifically, the estimation of the quadriceps ability to produce a torque on the tibia is complicated by the fact that the patella serves as an intermediary (a dynamic fulcrum) between the quadriceps and tibia. Therefore, the term effective quadriceps moment arm was coined to define the ability of the quadriceps to generate a torque on the tibia. Yet, this property has only been calculated two-dimensionally in the sagittal plane. The post-I external tibial rotation clearly demonstrates that acting through the patella, the VM effective moment arm has a component that results in internal tibial rotation. This study has advanced the clinical understanding of PFPS by providing a direct in vivo link between VMO weakness in isolation and knee joint kinematic alterations. In doing so it has demonstrated that VMO weakness is most likely a major factor in, but not the sole source of, PF maltracking. Thus, isolated VM strengthening will likely not fully correct PF maltracking in most individuals. In addition, it demonstrated that even with kinematic alterations in the PF and TF joint, pain was not experienced during the post-I trial, indicating that pain may be a factor that develops over time. Combining these findings with past results pertaining to the kinematics and bone shape alterations in individuals with PFPS supports two paths to PFPS in two kinematically unique subgroups. Such knowledge will likely help foster the next generation of treatments for PFPS that focus on first elucidating subject-specific factors leading to PF pain and then devising an intervention plan that specifically targets these factors in order to optimize treatment. Future work is required to provide further evidence on the validity of these paths and extend the current methodology to create a clinical diagnostic tool that will help guide therapeutic or surgical treatments for patients with PF pain. This work won the prestigious 2011 International Society of Biomechanics Clinical Award and the 2011 American Society of Biomechanics Clinical Award. Currently, the data from this study is being used as part of a cartilage contact analysis.